Diabetes is characterized by elevated blood glucose levels. Sustained elevation of blood glucose levels may affect proteins by a process known as glycation. Glycation is the non-enzymatic attachment of glucose to proteins and is considered a major pathophysiological mechanism causing tissue damage in diabetic subjects. Glycation involves the reaction of glucose and/or other reducing sugars with amino groups in proteins resulting in the formation of a Schiff base or aldimine. This labile adduct can tautomerize via the Amadori rearrangement to the more stable ketoamine.
Different glycated proteins have been identified in diabetic subjects, including albumin, hemoglobin and others. The function of glycated proteins may be impaired, depending on the location of the amino group(s) affected. For example, amino-terminal glycation of the 3-chains of hemoglobin gives rise to the glycated hemoglobins (HbA1c) in which responsiveness to 2,3-diphosphoglycerate is decreased and oxygen affinity increased. Glycation of the major thrombin inhibitor of the coagulation system, antithrombin III, decreases its affinity for heparin, and has been postulated to contribute to the hypercoagulable state associated with diabetes.
Measurement of the extent of protein “glycation” of certain proteins may be a valuable clinical tool to provide a more stable indicator of glycemic control than shorter term indicators such as measuring glucose levels directly, ultimately helping to improve the efficacy of treatments. The present inventors have previously shown that K41 glycation of CD59 is correlated to abnormal blood sugar levels and that glycation at K41 interferes with the normal activity of CD59 (U.S. Pat. Nos. 6,835,545; 7,049,082; and 7,439,330; the entire contents of each of which are incorporated herein by reference).
There remains, however, a need for improved methods of detecting and diagnosing diabetic conditions. In particular, certain patient populations may benefit from such improved methods. One such patient population includes pregnant women, who are at risk of developing gestational diabetes.